Accumulation of unfolded proteins in the endoplasmic reticulum triggers the unfolded protein response (UPR) pathway, which increases the expression of chaperones to maintain the homeostasis. Calreticulin is a calcium-binding chaperone located in the lumen of endoplasmic reticulum (ER). Here we show that in response to a UPR inducing reagent, tunicamycin, the expression of calreticulin (
crt-1) is specifically up-regulated in Caenorhabditis elegans. Tunicamycin (TM) induced expression of the
crt-1 requires IRE-1 and XBP-1 but is ATF-6 and PEK-1 independent. Analysis of the
crt-1 promoter reveals a putative XBP-1 binding site at the -284 to -278 bp region, which was shown to be necessary for TM-mediated induction. Genetic analysis of
crt-1 mutants and mutants of UPR pathway genes show various degrees of developmental arrest upon TM treatment. Our results suggest that the TM-induced UPR pathway culminates in the up-regulation of
crt-1, which protects the worm from deleterious accumulation of unfolded proteins in the ER. Knockdown of the
crt-1,
pdi-2, or
pdi-3 increased the
crt-1 expression, whereas knockdown of the
hsp-3 or
hsp-4 did not have any effect on
crt-1 expression, indicating the existence of complex compensatory networks to cope up with ER stress.